The overall objectives of this project are to develop further means for the therapeutic exploitation of both known and unappreciated biochemical and physiological differences which may exist between normal and neoplastic cells. Specific aims are: 1) to examine the nature of the mechanism of the observed LDH-Virus-induced inhibition of antibody synthesis or action, specifically as it may apply to the enhancement of asparaginase and related therapies; 2) to study the modulation effects that the LDH- Virus has on the malignant process; and 3) to determine the free amino acid patterns present in the physiological fluids and tissues of normal mice compared with those associated with various malignancies, as well as those animals undergoing enzymic and other therapies. More specifically, to determine the overall alterations occurring in the circulating amino acid pool when the host is exposed to the action of a specific enzyme such as asparaginase or glutaminase, or a combination of these and other potentially therapeutic enzymes. In addition to the above goals, we shall continue to explore the biological influence of newly developed enzymes which induce alterations in the circulating amino acid pool. The potential therapeutic properties of these new enzymes will be tested in vivo and the results will be correlated with the plasma and tissue levels of various free amino acids. Depletion or increases in amino acids, and the possible effects of enzyme metabolic products on the general physiology of the host, or upon the tumors, will be examined and efforts made to elucidate their mechanism of action.